Skip to main content
Log in

Suppression of experimental proliferative vitreoretinopathy by sustained intraocular delivery of 5-FU

  • Articles
  • Published:
International Ophthalmology Aims and scope Submit manuscript

Abstract

Treatment of proliferative vitreoretinopathy (PVR) requires a multidimensional approach. Recent studies have focused on pharmacologic techniques to inhibit intraocular cell proliferation by applying antimetabolite drugs. Side effects associated with these drugs and difficulties in achieving effective concentration inside the eye make drug delivery an important and difficult part of this approach. We have developed a sustained-release bioerodible device with modifiable release properties for intraocular drug delivery. In this study, we evaluated the efficacy of the device with two different concentrations of 5-fluorouracil (5-FU) in an experimental model of PVR in rabbit eyes. Both devices showed significant (P < 0.05) efficacy in prevention of PVR. Devices containing 20% 5-FU (total of 1 mg) were 100% effective in prevention of tractional retinal detachment. No significant complications, other than mild vitreous hemorrhage in a few cases, were associated with this method. Because pharmacologic therapy is used as an augmenting method to surgical therapy, these devices can be easily implanted inside the eye through a sclerotomy at the completion of surgery without any discomfort to patients. Slow release of drug by this method reduces the incidence of toxicity and increases the efficacy by providing a constant concentration of drug during the active period of the disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Blumenkranz MS, Ophir A, Claflin AJ, Hajek A. Fluorouracil for the treatment of massive periretinal proliferation. Am J Ophthalmol 1982; 94: 458–67.

    Google Scholar 

  2. Blumenkranz M, Hernandez E, Ophir A, Norton EWD. 5-fluorouracil: New applications in complicated retinal detachment for an established antimetabolite. Ophthalmology 1984; 91:122–30.

    Google Scholar 

  3. Koutsandrea CN, Miceli MV, Peyman GA, Farahat HG, Niesman MR. Ciprofloxacin and dexamethasone inhibit the proliferation of human retinal pigment epithelial cells in culture. cuit Eye Res 1991; 10: 249–58.

    Google Scholar 

  4. Chen EP, Steinhorst UH, Samsa GP, Saloupis PT, Hatchell DL. The effect of combined daunorubicin and triamcinolone acetonide treatment on a refined experimental model of proliferative vitreoretinopathy. Invest Ophthalmol Vis Sci 1992; 33: 2160–4.

    Google Scholar 

  5. Wiedemann P, Sorgente N, Bekhor C, Patterson R, Tran T, Ryan SJ. Daunomycin in the treatment of proliferative vitreoretinopathy. Effective doses in vitro and in vivo. Invest Ophthalmol Vis Sci 1985; 26: 719–25.

    Google Scholar 

  6. Barrada A, Peyman GA, Greenberg D, Stelmack T, Fiscella R. Toxicity of antineoplastic drugs in vitrectomy infusion fluids. Ophthalmic Surg 1983; 14: 845–7.

    Google Scholar 

  7. Wong VKW, Shapourifar-Tehrani S, Kitada S, Choo PH, Lee DA. Inhibition of rabbit ocular fibroblast proliferation by 5-fluorouracil and cytosine arabinoside. J Ocular Pharmacol 1991;7: 27–39.

    Google Scholar 

  8. Tano Y, Sugita G, Abrams G, Machemer R. Inhibition of intraocular proliferations with intravitreal corticosteroids. Am J Ophthalmol 1980; 89: 131–6.

    Google Scholar 

  9. Araiz JJ, Refojo MF, Arroyo MH, Leong FL, Albert DM, Tolentino FI. Antiproliferative effect of retinoic acid in intravitreous silicone oil in an animal model of proliferative vitreoretinopathy. Invest Ophthalmol Vis Sci 1993; 34: 522–30.

    Google Scholar 

  10. Ophir A. Further observations on the prevention of experimental proliferative vitreo-retinopathy by 5-fluorouracil. Ophthalmic Res 1991; 23: 128–32.

    Google Scholar 

  11. Stern WH, Lewis GP, Erickson PA, Guerin CJ, Anderson DH, Fisher SK et al. Fluorouracil therapy for proliferative vitreoretinopathy after vitrectomy. Am J Ophthalmol 1983; 96: 33–42.

    Google Scholar 

  12. Blumenkranz M, Ophir A, Claflin A. A pharmacologic approach to non-neoplastic intraocular proliferation. ARVO Supplement to Invest Ophthalmol Vis Sci. St. Louis: CV Mosby 1981:200.

    Google Scholar 

  13. Assil KK, Hartzer M, Weinreb RN, Nehorayan M, Ward T, Blumenkranz M. Liposome suppression of proliferative vitreoretinopathy: Rabbit model using antimetabolite encapsulated liposome. Invest Ophthalmol Vis Sci 1991; 32: 2891–7.

    Google Scholar 

  14. Stern WH, Guerin CJ, Erickson PA, Lewis GP, Anderson DH, Fisher SK. Ocular toxicity of fluorouracil after vitrectomy. Am J Ophthalmol 1983; 96:43–51.

    Google Scholar 

  15. Heidelberger C, Ansfield FJ. Experimental and clinical use of fluorinated pyrimidines in cancer chemotherapy. Cancer Res 1963; 23:1226–43.

    Google Scholar 

  16. Michels RG, Wilkinson CP, Rice TA. Complicated types of retinal detachment. In: Michels RG, Wilkinson CP, Rice TA, editors. Retinal detachment. St Louis: CV Mosby 1990: 677.

    Google Scholar 

  17. Rahimy MH, Borhani H, Peyman GA. Controlled-release delivery system for growth factors: Implications for retinal degenerative diseases. Invest Ophthalmol Vis Sci 1993; 34 Suppl: 1489.

    Google Scholar 

  18. Borhani H, Rahimy MH, Peyman GA. Sustained release of 5-FU from bioerodible-matrix delivery for intraocular application: In vitro and in vivo evaluation. Invest Ophthalmol Vis Sci 1993; 34 Suppl: 1488.

    Google Scholar 

  19. Chin S, Rahimy MH, Peyman GA. Bioerodible ganciclovir delivery system for intraocular application: In vitro kinetic evaluation. Invest Ophthalmol Vis Sci 1993; 34 Suppl: 1490.

    Google Scholar 

  20. Yang D, Rahimy DH, Peyman GA. Low molecular weight poly(caprolactone) and poly(DL-Lactide) prepared by hydrolysis and their applications as biodegradable carriers for drug delivery. Invest Ophthalmol Vis Sci 1993; 34 Suppl: 1493.

    Google Scholar 

  21. Mayerson PL, Hall MO, Clark V, Abrams T. An improved method for isolation and culture of rat retinal pigment epithelial cells. Invest Ophthalmol Vis Sci 1985; 26: 1599–609.

    Google Scholar 

  22. Fastenberg DM, Diddie KR, Sorgente N, Ryan SJ. A comparison of different cellular inocula in an experimental model of massive periretinal proliferation. Am J Ophthalmol 1982; 93: 559–64.

    Google Scholar 

  23. Siegel S. Nonparametric statistics for the behavioral sciences. New York: McGraw-Hill 1956: 312.

    Google Scholar 

  24. Shapiro MS, Thoft RA, Friend J, Parrish RK, Gressel MG. 5-Fluorouracil toxicity to the ocular surface epithelium. Invest Ophthalmol Vis Sci 1985; 26: 580–3.

    Google Scholar 

  25. Lee DA, Hersh P, Kersten D, Melamed S. Complications of subconjunctival 5-fluorouracil following glaucoma filtering surgery. Ophthalmic Surg 1987; 18: 187–90.

    Google Scholar 

  26. Liu KR, Peyman GA, She SC, Niesman MR, Khoobehi B. Reduced toxicity of intravitreally injected liposomeencapsulated cytarabine. Ophthalmic Surg 1989; 20: 358–61.

    Google Scholar 

  27. Barza M, Stuart M, Szoka F. Effect of size and lipid composition on the pharmacokinetics of intravitreal liposomes. Invest Ophthalmol Vis Sci 1987; 28: 893–900.

    Google Scholar 

  28. Stern WH, Heath TD, Lewis GP, Guerin CJ, Erickson PA, Lopez W et al. Clearance and localization of intravitreal liposomes in the aphakic vitrectomized eye. Invest Ophthalmol Vis Sci 1987; 28: 907–11.

    Google Scholar 

  29. Smith TJ, Pearson PA, Blandford DL, Brown JD, Goins KA, Hollins JL et al. Intravitreal sustained-release ganciclovir. Arch Ophthalmol 1992; 110: 255–8.

    Google Scholar 

  30. Sanborn GE, Anand R, Torti RE, Nightingale SD, Cal SX, Yates B et al. Sustained-release ganciclovir therapy for treatment of cytomegalovirusretinitis: Use of an intravitreal device. Arch Ophthalmol 1992; 110: 188–95.

    Google Scholar 

  31. Rubsamen PE, Davis PA, Hernandez E, O'Grady GE, Cousins SW. Prevention of experimental proliferative vitreoretinopathy with a biodegradable intravitreal implant for the sustained release of fluorouracil. Arch Ophthalmol 1994; 112:407–13.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Supported in part by U.S. Public Health Service grants EY07541 and EY02377 from the National Eye Institute, National Institutes of Health, Bethesda, MD, USA

Rights and permissions

Reprints and permissions

About this article

Cite this article

Borhani, H., Peyman, G.A., Rahimy, M.H. et al. Suppression of experimental proliferative vitreoretinopathy by sustained intraocular delivery of 5-FU. Int Ophthalmol 19, 43–49 (1995). https://doi.org/10.1007/BF00156419

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00156419

Key words

Navigation